Impact of antiviral therapy on the prevention of chronic viral infections.
Antiviral therapy has strongly reduced morbidity and mortality from chronic viral infections, and may also be used for preventing transmission. We study how most infections can be prevented using antiviral therapy at the lowest costs through transmission modelling, and we perform phylogenetic analysis of viral sequences to understand how chronic viral infections spread in populations.
Drug resistance to antiviral therapy.
The development and transmission of drug resistance viruses is a key challenge. The Department of Viroscience uses state-of-the-art in vitro virological, clinical and epidemiological studies to unravel the mechanisms of drug resistance and how drug resistance emerges and spreads within populations.
Therapeutic vaccinations as an alternative for antiretroviral treatment (ART).
ART is successful in suppressing HIV replication and disease progression, but needs daily medication to prevent viral rebound. By improving the immune responses against HIV, therapeutic vaccination tries to suppress HIV sufficiently without the need for regular ART. We have been exploring targets for HIV-specific cellular immune responses in vitro and in vivo. As a member of the European HIV Vaccine Alliance, we participate in phase I and II clinical trials. These trials are studying better markers of virus suppression and protection for future usage. In addition, therapeutic vaccinations may be combined with latency reversal therapy in a ‘shock and kill’ approach to eliminate the virus from the body.
Elimination of latent HIV provirus.
One approach to developing a cure is to activate latent provirus via latency reversal agents that specifically (re-)activate the virus, without a general immune activation. Various compounds that work directly on the viral LTR (or via epigenetic modifications) are currently being tested in vitro and in clinical trials. Measurements of the (infectious) reservoir are key in determining treatment success. Latency reversal is not currently considered to be sufficient to exhaust the viral reservoir, and should be complemented by immune clearance (e.g., via anti-viral therapy such as vaccination). We are collaborating with national and international partners to explore latency reversal and additional therapy.
